The Cardiac Arrhythmia Suppression Trial II - CAST-II

Description:

Moricizine for mortality after myocardial infarction.

Hypothesis:

CAST II evaluated moricizine during a 14 day post myocardial exposure and during a long-term phase that tested moricizine's ability to reduce mortality after myocardial infarction when ventricular premature depolarizations were either adequately suppressed or partially suppressed by the drug. The specific hypotheses tested was that suppression of arrhythmia by Moricizine would decrease mortality.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 1,325
Mean Follow Up: 18 months
Mean Patient Age: 62
Female: 17
Mean Ejection Fraction: 32%

Patient Populations:

Ambulatory electrocardiographic recording obtained 4-19 days after acute MI demonstrated six ventricular depolarizations per hour
Left ventricular ejection fraction < 40%

Exclusions:

Ventricular arrhythmias causing syncope or presyncope
Ventricular tachycardia with 15 or more successive beats at a rate of > 120 beats per minute
Poor patient compliance
Contraindication to antiarrhythmic drug therapy

Primary Endpoints:

Death or cardiac arrest within 2 weeks of beginning moricizine
Death due to arrhythmia
Cardiac arrest due to arrhythmia requiring resuscitation

Secondary Endpoints:

Tolerability of moricizine

Drug/Procedures Used:

Moricizine, 200mg tid titrated up to 900mg daily based on arrhythmia suppression (80% of ventricular premature depolarizations or 90% of runs of nonsustained ventricular tachycardia).

Concomitant Medications:

Beta blockers (29%)
Calcium channel blockers (41%)
Digitalis (27%)
Nitrates (46%)
Diuretics (42%)
Antihypertensives (36%)

Principal Findings:

CAST-II stopped early because the first 14 day period of treatment with moricizine after myocardial infarction was associated with excess mortality.

At completion of the long-term phase there were 49 deaths or cardiac arrests due to arrhythmias in patients assigned to Moricizine versus 42 in placebo group (p = .40).

Interpretation:

"As with the antiarrhythmic agents used in CAST (flecainide and encainide), the use of moricizine in CAST-II to suppress asymptomatic or mildly symptomatic ventricular premature depolarizations to try to reduce mortality after myocardial infarction is not only ineffective but also harmful." (From Abstract)

References:

1. N Engl J Med 1992;327:227-33. Final results
2. Control Clin Trials 1994;15:437-49. Quality of life

Clinical Topics: Arrhythmias and Clinical EP, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias

Keywords: Encainide, Myocardial Infarction, Tachycardia, Ventricular, Ventricular Fibrillation, Moricizine, Stroke Volume, Heart Arrest, Flecainide, Ventricular Premature Complexes


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